N-acetylgalactosaminyl transferase-3 is a potential new marker for non-small cell lung cancers.

Abstract

N-acetylgalactosaminyl transferase-3 (GalNAc-T3) is an enzyme involved in the initial glycosylation of mucin-type O-linked proteins. In the present study, we used immunohistochemistry to examine GalNAc-T3 expression in 215 surgically resected non-small cell lung cancers. We analysed the biological and clinical importance of GalNAc-T3 expression, especially with regard to its potential as a prognostic factor. We found that normal bronchial epithelial cells, bronchial gland cells, and alveolar pneumocytes showed cytoplasmic immunostaining for GalNAc-T3. Low expression of GalNAc-T3, observed in 93 of 215 tumours (43.4%), was found more frequently in tumours from smokers than those from nonsmokers (P=0.001), in squamous cell carcinomas than nonsquamous cell carcinomas (P<0.0001), and in moderately and poorly differentiated tumours than well differentiated tumours (P=0.0002). Multivariate logistic regression analysis showed that an association of low GalNAc-T3 expression with squamous cell carcinomas was the only one significant relationship of GalNAc-T3 expression with various factors (P<0.0001). Moreover, tumours losing GalNAc-T3 expression had a significantly higher Ki-67 labelling index than tumours retaining GalNAc-T3 expression (P=0.0003). Patients with low GalNAc-T3 expression survived a significantly shorter time than patients with high GalNAc-T3 expression in 103 pStage I non-small cell lung cancers (5-year survival rates, 58% and 78%, respectively; P=0.02 by log-rank test) as well as in 61 pStage I nonsquamous cell carcinomas (5-year survival rates, 63% and 85%, respectively; P=0.03). Low GalNAc-T3 expression was an unfavourable prognostic factor in pStage I non-small cell lung cancers (hazards ratio, 2.04; P=0.03), and in pStage I nonsquamous cell carcinomas (hazards ratio, 2.70; P=0.03). These results suggest that GalNAc-T3 is a new marker of non-small cell lung cancers with specificity for histology and prognosis.

• Authors: H Dosaka-Akita, I Kinoshita, K Yamazaki, H Izumi, T Itoh, H Katoh, M Nishimura, K Matsuo, Y Yamada, K Kohno
• Journal: British journal of cancer (Br J Cancer) Vol. 87 Issue 7 Pg. 751-5 (Sep 23 2002) ISSN: 0007-0920 [Print] England
• PMID: 12232759 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• N-Acetylgalactosaminyltransferases

Topics

• Aged
• Biomarkers, Tumor (analysis)
• Blotting, Western
• Carcinoma, Non-Small-Cell Lung (diagnosis, enzymology, pathology)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Lung Neoplasms (diagnosis, enzymology, pathology)
• Male
• Middle Aged
• N-Acetylgalactosaminyltransferases (metabolism)
• Neoplasm Staging
• Predictive Value of Tests
• Proportional Hazards Models
• Smoking
• Survival Analysis